Implantable infusion devices provide a patient with an vivo source of a drug to be administered, in a device which permits controlled delivery of the drug over a predetermined time period. Certain drugs, such as, for example, chemotherapy drugs and opioids, may be most effective if administered at a constant dose rate, instead of at discrete intervals.
A typical infusion device or pump includes a hermetically sealed outer housing which holds a vapor pressure fluid or other means for exerting a compressive force on a compressible or flexible inner drug reservoir which communicates with a drug delivery port. Alternatively, the drug may be disposed in the outer housing, with a propellant disposed in the inner housing. When the outer housing is filled with the drug, the propellant in the inner housing is compressed and changes state from a vapor to a liquid, thereby recharging the driving mechanism of the device. In still other embodiments, the outer housing may be divided into two chambers separated by a liquid-impermeable diaphragm. One chamber contains the drug and includes a drug delivery port, and the other chamber contains a propellant or spring member for exerting a force against the diaphragm so as to expel the drug through the delivery port.
The infusion device must meet numerous requirements for safety and efficacy. For example, the housing material must not react with body fluids or with the drugs and propellants inside the housing. Further, the membrane or flexible barrier between the chambers must not leak and must be impermeable to gas-phase fluids so as to prevent contamination of the drug with the propellant. Since the device is designed for implantation into a patient, great care must be taken to prevent any leakage of either the drug or the propellant into the patient's body. In addition, the device is desirably as small and lightweight as possible so as to cause minimum invasive trauma, discomfort and disfigurement to the patient, yet sufficiently large to provide a useful therapeutic dosage of the drug being administered and minimize the frequency with which the device must be recharged. It is desirable to make the pump refillable so that it need not be surgically removed and replaced when the drug is depleted. However, refillability of the pump requires a port which is either outside of the skin or transcutaneously accessible without introducing infection or risking the release of an excessive and potentially harmful amount of the drug into the patient. Also, in those devices in which a propellant is contained within a flexible bag which expands and contracts in response to changes in the propellant pressure, it is necessary to ensure that introduction of the drug to the drug reservoir surrounding the propellant bag is not impeded by the presence and location of the bag in the reservoir and/or does not puncture or pinch the bag. Thus, it may be necessary to affix the repellant chamber or bag to the housing so as to avoid such problems. There is the additional problem of ensuring that the drug reservoir can be fully depleted and refilled, for optimum efficiency of the device.
Administration of a desired dosage of a drug over a period of time may require a controllable, constant flow of the drug from the device. However, as the drug is depleted from the reservoir, or if the force exerted on the drug reservoir cannot be controlled, a constant dose rate may be difficult to sustain.
U.S. Pat. No. 3,840,009 to Michaels et al. discloses a vapor pressure drug delivery device which has two chambers separated by a flexible wall or bladder. The outer chamber contains a drug to be administered to a patient, and the inner chamber contains a pressure fluid which expands to conform to the shape of the outer chamber, thereby enabling expulsion of substantially all of the drug within the outer chamber. The pressure fluid is maintained at a positive pressure at the temperature at which the device is used, so that no external power source is required.
U.S. Pat. No. 5,167,633 to Mann et al. discloses a medication infusion pump in which a constant pressure is exerted on a liquid medication to be administered. The pump includes a pressure reservoir in the form of a hollow enclosure with at least one flexible wall for containing a pressure fluid. The medication to be administered is outside of the pressure reservoir. The pressure fluid undergoes a phase change from a liquid to a vapor so as to expel the drug from the pump. The Mann et al. device is maintained at a negative pressure at the temperature of use to avoid leakage of medication from the pump into the patient.
U.S. Pat. No. 5,514,103 to Srisathapat et al. discloses a medication infusion pump including a drug reservoir and a pressure fluid reservoir which are separated by a movable wall or flexible bag. The pressure fluid reservoir includes a spacer therein to prevent contraction of the pressure fluid reservoir below a minimum volume which is slightly greater than the liquid phase volume of the pressure fluid, so that a portion of the pressure fluid always remains in a vapor phase. As a result, even when the drug reservoir is completely filled, the pressure fluid is not entirely in the liquid phase. Thus, additional energy to reinstate a vapor phase is not required.
U.S. Pat. No. 3,951,147 to Tucker et al. discloses a refillable implantable infusate pump in which a bellows containing a drag is contained within a housing which is filled with a pressure fluid or propellant. The Tucker et al. pump includes a filtering chamber to ensure removal of debris from the infusate drug prior to its delivery to the patient.
U.S. Pat. No. 5,045,064 to Idriss discloses a constant pressure implantable pump which employs shape-memory metal bands around a reservoir containing a fluid to be infused. The bands compress the reservoir containing the fluid to be infused, thereby eliminating the need for a propellant.
U.S. Pat. No. 5,395,324 to Hinrichs et al. discloses an infusion pump having a primary entry port leading to a drug reservoir, a separate bolus port leading to a bolus chamber, and means for ensuring that the bolus chamber is not inadvertently filled with the drug intended for the primary drug reservoir.
U.S. Pat. No. 5,769,823 to Otto discloses implantable infusion pump which comprises a plastic housing, a bellows chamber enclosing a propellant, and two separate resilient plastic bags enclosing an infusate. The bags are surrounded by glycerin or the like which binds with any propellant passing through the bellows wall into the housing, thereby preventing passage of the propellant through the housing into the patient.
U.S. Pat. No. 5,575,770 to Melsky et al. discloses an implantable infusion pump having 4 valve-actuated bolus delivery chamber. Inadvertent administration of an overdose to the patient through the bolus delivery chamber is prevented by a design which requires the use of a side-access delivery needle, which is inserted through a pair of septa which are spaced apart to define a bolus chamber. The tip of the needle extends beyond the lower septum and depresses a lever to actuate the normally-closed valve. The side opening of the needle is disposed between the septa in lo the bolus chamber for delivery of the bolus dose to the bolus chamber. The design prevents erroneous dose delivery by requiring the simultaneous opening of the valve with delivery of the drug into the bolus using a side-access delivery needle.
It would be advantageous to provide an implantable infusion pump which is of simple construction and operation, made of lightweight materials, inexpensive to manufacture, efficient in the delivery of medicine, and easy to refill.